Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A chromogenic two-stage assay for human tryptase, a specific marker of mast cell activation, was developed based on the tryptase-induced conversion of prothrombin to thrombin. This assay proved to be more sensitive and reliable than measurements of amidolytic activity of tryptase with small synthetic substrates such as Bz-Arg-Nan and was suitable to detect tryptase activity in human body fluids. In addition, the assay was useful for studies of natural and recombinant inhibitors of tryptase.
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PMID:A new, highly sensitive enzymic assay for human tryptase and its use for identification of tryptase inhibitors. 220 44

Human mast cells can be divided into two subsets based on serine proteinase composition: a subset that contains the serine proteinases tryptase and chymase (MCTC), and a subset that contains only tryptase (MCT). In this study we examined both types of mast cells for two additional proteinases, cathepsin G and elastase, which are the major serine proteinases of neutrophils. Because human mast cell chymase and cathepsin G are both chymotrypsin-like proteinases, the properties of these enzymes were further defined to confirm their distinctiveness. Comparison of their N-terminal sequences showed 30% nonidentity over the first 35 amino acids, and comparison of their amino acid compositions demonstrated a marked difference in their Arg/Lys ratios, which was approximately 1 for chymase and 10 for cathepsin G. Endoglycosidase F treatment increased the electrophoretic mobility of chymase on SDS gels, indicating significant N-linked carbohydrate on chymase; no effect was observed on cathepsin G. Immunoprecipitation and immunoblotting with specific antisera to each proteinase revealed little, if any, detectable cross-reactivity. Immunocytochemical studies showed selective labelling of MCTC type mast cells by cathepsin G antiserum in sections of human skin, lung, and bowel. No labeling of mast cells by elastase antiserum was detected in the same tissues, or in dispersed mast cells from lung and skin. A protein cross-reactive with cathepsin G was identified in extracts of human skin mast cells by immunoblot analysis. This protein had a slightly higher Mr (30,000) than the predominant form of neutrophil cathepsin G (Mr 28,000), and could not be separated from chymase (Mr 30,000) by SDS gel electrophoresis because of the size similarity. Using casein, a protein substrate hydrolyzed at comparable rates by chymase and cathepsin G, it was shown that about 30% of the caseinolytic activity in mast cell extracts was sensitive to inhibitors of cathepsin G that had no effect on chymase. Hydrolytic activity characteristic of elastase was not detected in these extracts. These studies indicate that human MCTC mast cells may contain two different chymotrypsin-like proteinases: chymase and a proteinase more closely related to cathepsin G, both of which are undetectable in MCT mast cells. Neutrophil elastase, on the other hand, was not detected in human mast cells by our procedures.
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PMID:Identification of a cathepsin G-like proteinase in the MCTC type of human mast cell. 221 56

We have used fiberoptic bronchoscopy to obtain endobronchial biopsies in which mast cells and eosinophils were enumerated using monoclonal antibodies directed against mast cell tryptase (AA1) and the eosinophil cationic protein (EG2). Eleven symptomatic atopic asthmatics treated with beta 2-agonists alone and six normal subjects were studied. Over a period of 2 wk prior to bronchoscopy, patients recorded asthma symptom scores, bronchodilator usage, and twice-daily peak expiratory flow. Five days before bronchoscopy, methacholine responsiveness was assessed. Two biopsies were taken from the subcarinae, one of which was processed into araldite for immunostaining by the streptavidin biotin immunoperoxidase method and the other into Spurr resin for electron microscopy. The number of AA1 staining mast cells present in the bronchial mucosa was not significantly different in the epithelium or submucosa between the asthmatic and the normal subjects. However, in the biopsies from asthmatics, there were significantly greater numbers of EG2-staining eosinophils in the epithelium (median, 1.2/mm versus zero; p less than 0.005) and in the submucosa (median, 50/mm2 versus 1/mm2; p less than 0.001). Electron microscopy showed morphologic features of mast cell and eosinophil degranulation in the asthmatics. No correlation could be established between mast cell or eosinophil numbers and indices of disease activity of PC20 methacholine, which points to the complexity of mechanisms responsible for the symptoms and the airway hyperresponsiveness of asthma.
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PMID:Quantitation of mast cells and eosinophils in the bronchial mucosa of symptomatic atopic asthmatics and healthy control subjects using immunohistochemistry. 202 38

The susceptibility of connective tissue elements to degradation by human mast cells was explored using purified mast cell tryptase and sonicated mast cell preparations. The R-22 strain of smooth muscle cells from rat heart was used for preparation in vitro of a labelled anchored matrix. Digestion of 11.9 +/- 1.2% (n = 5) of this matrix was observed after overnight incubation with the mast cell sonicates. Pretreatment of the sonicate with a tryptase inhibitor TLCK reduced the digestion by 42%. Digestion of 12 +/- 1% (n = 4) of the matrix was observed with purified tryptase. The susceptible substrate within this anchored insoluble matrix resided in the glycoprotein compartment as defined by enzymatic characterization of the residual matrix. Mast cells may play a role in mediating connective tissue degradation through the release of proteases specifically synthesized by this cell.
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PMID:The mast cell as an effector of connective tissue degradation: a study of matrix susceptibility to human mast cells. 222 42

Tryptase, a mediator secreted by human mast cells during immediate reactions, has demonstrated effects on several pathways in vitro. This enzyme can rapidly inactivate fibrinogen and, as a complex with heparin, may prevent coagulation that may otherwise occur when plasma enters tissues at sites of immediate reactions. Tryptase may also activate prostromelysin, which in turn activates latent collagenase. When canine pulmonary smooth muscle is incubated with canine tryptase, the contractile response to histamine is increased. Tryptase, quantifiable in complex biologic fluids by immunoassay, can serve as a specific indicator of mast cell involvement in certain clinical settings. For example, after bee sting--induced anaphylaxis, tryptase levels in the blood peak at approximately 1 hour, then decline with a half-life of approximately 2 hours. Additionally, elevated tryptase levels in bronchoalveolar lavage fluid of asymptomatic, atopic persons with asthma suggest ongoing mast cell activation, which may relate to adenosine hyperresponsiveness and a persistence of bronchial hyperreactivity. Tryptase levels in bronchial lavage fluid of atopic patients with asthma rise markedly after endobronchial allergen challenge but not after an exercise challenge, suggesting a lack of mast cell involvement in the latter condition.
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PMID:Tryptase, a mediator of human mast cells. 222 22

Two types of mast cells were previously defined based on neutral protease composition and ultrastructurally distinguished by granule morphology. The MCT cell contains tryptase with little, if any, chymase and was noted to have varying numbers of irregularly-shaped granules with discrete scrolls or particulate or beaded material. The MCTC cell contains both tryptase and chymase and was noted to have more regularly-shaped electron-dense granules with characteristic grating or lattice substructures. This study reports the use of electron microscopy and immunogold staining with antibodies against tryptase and chymase to demonstrate in mature unstimulated MCTC cells in situ, the focal occurrence of discrete or complete scrolls in peripheral regions of certain granules where chymase is deficient. these scrolls often appeared to be protruding from the granule. Granules containing discrete scrolls were observed in 10 of 340 mature MCTC cells, accounting for less than 1% of MCTC granules. Other granules in such cells as well as other regions of the granule under consideration, showed strong staining for both tryptase and chymase. These results strengthen the association of morphology with protease composition in human mast cell secretory granules, but weaken the use of morphology alone to identify the MCTC and MCT types of human mast cells. Whether the uncommon occurrence of focal absence of chymase in MCTC cells arises by chance or as a result of factors relating to mast cell development, interconversion, activation, or regranulation will require further clarification. In conclusion, the appearance of grating or lattice structures in mast cells indicates the presence of chymase and tryptase, characteristic of the MCTC phenotype, whereas multiple discrete scrolls in irregularly shaped granules suggests the MCT phenotype.
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PMID:Human MCTC type of mast cell granule: the uncommon occurrence of discrete scrolls associated with focal absence of chymase. 223 9

Tissue mast cells play a central role in immediate hypersensitivity reactions. The clinical manifestations of these reactions appear to be dependent, in large part, on the anatomic location of the stimulated mast cells and the type of mediators released. In vivo and in vitro studies indicate that the tissues in which mast cells reside may greatly influence their biochemical composition, expression of surface receptors, and response to potential stimuli. Although all human mast cells in different organs store similar concentrations of histamine, heparin, and tryptase, cutaneous mast cells appear to be the predominant source of mast cell-derived chymase. Furthermore, at the time of stimulation, human skin mast cells predominantly form PGD2, whereas lung and intestinal mast cells generate LTB4, LTC4, and PGD2. Functional studies indicate that human cutaneous mast cells differ from human lung, heart, and intestinal mast cells. Skin mast cells are responsive to a variety of immunologic and nonimmunologic stimuli in vitro, whereas human pulmonary, cardiac, and intestinal mast cells are relatively refractory to many of these stimulatory signals. Taken together, these observations indicate that mast cells may assume different, and possibly specialized, functions within a specific tissue. Such site-to-site variation potentially could have important clinical significance, to the extent that information gained from mast cells in one organ may not be applicable to a mast cell population in a different tissue. Furthermore, these differences among human mast cells may not be confined to their biochemical composition and responses to various stimuli, but also may extend to the effectiveness of different anti-allergic preparations. Therefore, these observations underscore the importance of continued detailed investigation of human mast cells from different anatomic sites.
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PMID:IgE and immediate hypersensitivity. 224 56

An avidin-biotin enhanced immunoperoxidase procedure using monoclonal antibodies (AA1, AA3, and AA5) prepared against human mast cell tryptase resulted in intense staining of mast cells in paraffin-embedded tissue. The distribution of mast cells observed was similar to that seen when adjacent serial sections were stained using a standard procedure with toluidine blue, though the immunoperoxidase technique permitted the identification of significantly more mast cells. With monoclonal antibody AA1, immunostaining was entirely specific for mast cell granules, and there was negligible background staining in a range of tissues including lung, tonsil, colon, gastric mucosa, skin, and pituitary. There was no staining of antibody on basophils or on any other normal blood leukocyte. The technique was effective with tissue fixed in either Carnoy's or neutral buffered formalin, though the internal mast cell structure was better preserved with formaldehyde fixation. The immunoperoxidase staining procedure with monoclonal antibody AA1 is a highly specific and sensitive means for the detection of mast cells in routinely processed tissues.
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PMID:Immunohistochemical identification of mast cells in formaldehyde-fixed tissue using monoclonal antibodies specific for tryptase. 225 Jan 89

Lesional (n = 15) and non-lesional (n = 10) skin of subjects with mastocytosis was analysed for the distribution and concentration of trypase positive, chymase negative mast cells (MCT) and tryptase positive, chymase positive mast cells (MCTC) cells and compared to normal skin (n = 23) and non-lesional skin of subjects with unexplained anaphylaxis or flushing episodes (n = 6). Skin biopsies were fixed in Carnoy's fluid and subjected to double immunohistochemical staining with biotinylated mouse monoclonal anti-chymase antibody followed by alkaline phosphatase-conjugated mouse monoclonal anti-tryptase antibody. MCTC cells were the only type of mast cells seen in all specimens analysed and in each case were more numerous in superficial compared to deep regions of dermis. The concentration (mean +/- s.d.) of mast cells in the superficial dermis of mastocytosis lesions (40 985 +/- 21 772 mast cells/mm3) was significantly increased over that in corresponding areas of non-lesional skin from subjects with mastocytosis (7178 +/- 3607 mast cells/mm3), skin from subjects with idiopathic anaphylaxis or flushing episodes (6974 +/- 3873 mast cells/mm3) and normal skin (7347 +/- 2973 mast cells/mm3). The exclusive presence of MCTC cells in skin lesions of mastocytosis which are characterized by non-malignant hyperplasia of mast cells suggests involvement of local tissue factors in mast cell recruitment and differentiation.
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PMID:Mast cells in cutaneous mastocytosis: accumulation of the MCTC type. 231 Sep 82

Intestinal mucosal damage and restitution were examined following antigen-induced systemic anaphylaxis in Nippostrongylus brasiliensis immunized rats. The rats were injected intravenously with N. brasiliensis antigen or saline. At 60 min, morphological and biochemical parameters were determined in jejunum and ileum, and the epithelial permeability was assessed by measuring recovery of 51Cr-ethylenediaminetetraacetic acid in the blood after injecting it into a ligated segment. Antigen challenge resulted in significant abnormalities: (1) villus damage with sloughing of enterocytes; (2) decreased activities of brush border enzymes; (3) decreased levels of mucosal histamine and rat mast cell protease II (mast cell mediators), and (4) increased uptake of 51Cr-ethylenediaminetetraacetic acid. Progression of the injury was examined by taking consecutive biopsies at 15-min intervals for 60 min and then at 5 h. At 15 min, an abnormality was present in all sections which ranged from minor oedema and enterocyte detachment at villus tips to virtual complete destruction of the apical region. Restitution occurred by villus contraction with migration of the epithelium over the damaged regions. At 5 h, the epithelium had resealed, but the villi were significantly reduced in height.
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PMID:Antigen-induced mucosal damage and restitution in the small intestine of the immunized rat. 235 70


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